Nitroalkyl dihalocarbanilates



nits: r sent 3fi29273 Patented Apr. l0, 1%62 NITROALKYL The invention relates to new and to the process of making the same.

The invention also relates to certain compositions comprising (l) a cleansing compound such as soap or other organic cleansing detergent including either anionic or non-ionic surface active detergents and mixtures thereof; and (2) an antiseptic amount and more specifically a bacteriostatic amount of these new compounds.

Numerous compounds are known in the art which will serve as effective antiseptics or bacteriostats. However, it has also been observed in compositions containing these compounds combined with a detergent, that the latter tends to destroy or greatly vitiate this antiseptic or bacteriostatic effect. In addition to such compounds not losing this antiseptic or bacteriostatic activity in the presence of a detergent, these compounds should not be toxic, should not irritate the human skin, should not impart any color or odor to the detergent, and should have affinity for the skin whereby a small amount will remain and exert an antiseptic and bacteriostatic effect.

It is, therefore, an object of this invention to provide new compounds which have utility as antiseptics and particularly exhibit bacteriostatic properties. A further object is to provide new compositions, which when mixed with a detergent, retain their antiseptic or bacteriostatic properties. A further object is to provide new antiseptic compounds which are non-irritating when combined with detergents and do not impart any color or odor thereto. A still further object is to provide antiseptic and bacteriostatic compositions for controlling the growth of bacteria such as Micrococcus pyogenes var. our-ens on surfaces containing the same. Additional objects will be evident from the description that follows.

The new compounds of this invention may be represented by the general formula useful compounds and where X is a halogen selected from the group consisting of chlorine and bromine, Y is a member selected from the group consisting of hydrogen, chlorine and bromine and Q is a mono-nitroalkyl radical having from 3 to 8 carbon atoms. Representative of the compounds of this invention are l-(2-nitrobutyl) 3,4-dichlorocarbanilate, 1-(Z-nitro-Z-methylpropyl) 3,4-dichlorocarbanilate, 4-(3- nitroheptyl) 3,4-clichlorocarbanilate, 3-(2-nitro-2-methylhexyl) 3,4-dichlrocarbanilate, 1(2-nitroamyl) 3,4-dichlorocarbanilate, 4- 5 -nitro octyl 3,4-dlchlorocarbanilate, 1-(3-nitrohexyl) 3,4-dichlorocarbanilatc, I-(Z-nitropropyl) 3,4-dichlorocarbanilate, l-(Z-nitrobutyl) 3,4-dibromocarbanilate, 1-(Z-nitro-Z-methylpropyl) 3,4,5-trichlorocarbanilate, 4-(3-nitroheptyl) 3,4-dibromocarbanilate, 4-(5-nitrooctyl) 3,4-dibromocarbanilate, 3-(2-nitro- Z-rnethylhexyl) 3,4,5-trichlorocarbanilatc, and the like.

in general the process of making the new compounds of this invention involves the reaction of a polyhalophenylisocyanate with the desired nitroalcohol, which latter type of compound is well known as a class of chemical compounds. The following examples are illustrative of the process.

EXAMPLE I Z- (Z-Nitrobutyl) 3,4-Dichlorocarbanilate A mixture of 18.8 g. (0.1 mole) 3,4-dichlorophenylisocyanate and 11.9 g. (0.1 mole) 2-nitro-1-butanol is gently warmed in a flask of -50". An exothermic reaction sets in and the temperature is held at. 60-65 using an ice bath. The contents of the flask solidify upon completion of the reaction. Recrystallization of the product from 60% ethanol gives fine colorless needles (MP. 1Z1.4i22.1 C.) yield: 88.6% of theory. Analysis percent 1 =calculated 9.12; found 9.07.

Following the procedure of Example 1 but. using 18.8 g. (0.1 mole) 3,4-dichloropbenylisocyanate and 11.9 g. (0.1 mole) Z-methyl-Z-nitro-l-propanol, small colorless needles of l(2-methyl-2-nitropropyl) 3,4-dichlorocarhanilate are recrystallized from 60% ethanol (MP. ll4.2ll5.l C.) yield: 98.0% theory. Analysis percent Cl: calculated 23.08; found 22.91.

EXAMPLE 1V 3- (2-MelhyZ-Z-Nitrohexyl BntyZ(3,4-Dichlor0- carbaizi late) Following the procedure of Example 1 but using 16.1 g. (0.1 mole) 2-uitro-2methyl'3-hexanol as the alcohol, small white granules of 3-(Z-methyl-Z-nitrohexyl) butyl 3,4-dichlorocarbanilate are recrystallized from 90% ethanol (MP. 8.3 99.2 C.) yield 99.2% theory. Analysis percent Cl: Calculated 20.30; found 20.99.

EXAMPLE V 4-(3-Jitroheptyl) 3,4-Dichlorocarbanilate Following the procedure (0.1 mole) 3-nitro-4-heptanol, small White granules of 4-(3-nitroheptyl) 3,4-dichlorocarbanilate are recrystallized from heptane (MP. 1148-1155 C.) yield: 80.0% theory. Analysis percent Cl: calculated 20.30; found 20.46.

EXAMPLE V1 4- (5 -Nitro0clyl) 3,44)icizlorocarbanilme Following the procedure of Example I but using 17.5 g. (0.1 mole) 5-nitro-4-octanol as the alcohol, white granules of 4-(5-nitrcoctyl) 3,4-dichlorocarbanilate are obtained in good yields.

EXAMPLE VII 1 -(2-Nitr0bziryl) 3,4,5 -T rich loroca'rbanilate Employing the procedure of Example I but using 22.4 g.

(0.1 mole) 3,4,5-trichlorophenylisocyanatc in place of the 3,4-dichlorophenylisocyanate, I-(Z-nitrobutyl) 3,4,5-trichlorocarbanilate is obtained in good yield.

From the above examples it will be noted. that in a preferred method of preparing the new compounds of this invention, substantially equimolecular proportions of a polyhalophenylisocyanate and the appropriate mononitroalcohol are mixed and gently heated usually in the range of 45 to C. An exothermic reaction sets in and it has been found desirable to maintain the reaction temperature around C. to C. by means of an ice bath during the reaction period of about /2 to 1 hour.

of Example I but using 16.1 g.

a: Upon completion of the reaction, the desired nitroalkyi polyhalocarbanilate is then recrystallized from an appropriate solvent such as ethanol. However, depending on the particular alcohol used, the mixture of polyhalophenylisocyanate and the nitroalcohol v ill react in certain instances at room temperature of about C. to temperatures up to 80 (2. with reaction periods up to 4 hours. In addition other solvents may be used for recrystallization of the product such as xylene, benzene, heptane, and the like.

The compounds of this invention having the general formula given above have been found to have excellent antiseptic properties and more particularly exhibit bacteriostatic properties when mixed with cleansing compounds or detergents in cleansing compositions. The term detergent as used in this patent application has reference to any of the following classes of cleansing compounds and mixtures thereof: soaps and other anionic surface active detergents plus non-ionic surface active detergents.

The term soap is employed in its popular meaning and refers to cleansing compounds usually made by the action of an alkali or fat or fatty acids, e.g., the sodium or potassium salts of either saturated or unsaturated fatty acids. By way of example each of the compounds described in Examples I, III, IV and V above were separately incorporated in a neutral high grade white soap (3 mixture of 80 percent sodium soap and 20 percent potassium soap produced from a 70 percent tallow and percent oil glyceride blend in accordance with US. Patent 2,2955%) in a weight ratio of two parts to 100 parts by weight soap. Aliquots of each were added to a Saborauds dextrose agar medium so as to give concentrations of the com pounds in the agar as set forth in Table )1 below. The agar in each case was then poured into a petri dish, allowed'to harden, and then innoculated with a standard culture of the bacterium Micrococcus pyrogenes var. aureus of standard resistance. The incubation in each instance was made simultaneously at 37 C for 48 hours. The extent of growth is noted below:

TABLE I Concentratiompartsper lOT 1W 5M 10M 50M c 2nltr0buty1 4-mtrocarbanilate Legend:

1T thousand 2M million +=growth -=no growth The Group B compounds were included in the above table to point up the importance of the placement and number of chlorine and nitro substituents in the molecule of the carbauilate compounds of this invention.

It is to be understood that the use of the nitroalkyl dichlorocarbanilates with soap, as set forth in the above table, is merely illustrative and that these compounds may also be used with other soaps and other anionic surface active and non-ionic surface active organic detergents and have proven equally effective therein. Other alkali metal soaps of higher fatty acids of animal or vegetable origin may be used such as stearic, lauric, palmitic, oleic, linoleic, ricinoleic, and the like, including mixtures therea; of obtained from tallow, lard, coconut oil, palm oil, castor oil, olive oil, hydrogenated fish and cottonseed" oils and the like.

The organic anionic detergents of this invention in clude in addition to the alkali metal fatty acid soaps the well known surface active alkali metal sulfonates and sulfates. Representative of these are the long chain alkyl aryl sulfonates, i.e. those wherein the alkali radical is straight or branched in structure and contains from 8 to 22 carbon atoms, but preferably 10 to 16 carbon atoms, examples of which are octyl, decyl, dodecyl, keryl, penta decyl, hexadecyl, octadecyl, mixed long chainalkyls de' rived from long chain fatty materials such as the lauryl radical, cracked paraffin wax olefins, polymers of lower mono-olefins such as propylene tetramer and the. like, and wherein the aryl radical is derived from benzene, toluene, xylene phenol, the cresols, naphthalene, and the like. Specific examples of such comprise sodium dccyl benzene sulfonate, sodium dodecyl benzene sulfonate, sodium lauryl benzene sulfonate and sodium hexadecyl benzene sulfonate. Further descriptive information regarding these compounds may be found in US. Patent 2,264,737.

Other sulfonate surface-active agents are also contemplated, e.g. the long chain alkyl sulfonates such as sodium hexadecane sulfonate and sodium octadecane sulfonate.

The well known sulfate detergents having 12 to 26 carbon atoms and particularly those having an alkyl radical of about 8 to 22 carbon atoms may be employed as anionic detergent bases in accordance with this invention. Such detergents include the sulfuric semesters of polyhydric alcohols incompletely esterified with fatty acids, e.g'. sodium coconut oil monoglyceride mono-sulfate, sodium tallow diglyceride mono-sulfate, the pure and mixed higher alkyl sulfates such as sodium lauryl sulfate and sodium cetyl sulfate.

Additional anionic surface active sulfonates and sulfates contemplated by this invention are the sulfated and sulfonated alky-l acid amides such as lgepon T (RCOOCHgSOgNH where R is an alkyl radical containing from 12 to 18 carbon atoms), sodium salt of the bisulfate of a dia kyl dicarboxylate, sodium salt of the sulfonic acid derivative of a dialkyl dicarboxylate, sodium sulfosuccinic esters such as NaOOCCI-I CH(SO N21) CONHC H and the like.

In addition to the organic anionic detergents, the nonionic surface-active agents containing the desired nitroalkyl dichlorocarbanilate derivatives provide efiective bacteriostatic cleaning compositions. The non-ionic surface active agents contemplated are viscous liquid to wax-like water-soluble surface-active substances containing a polyglycol eLher group of the structure R-(CH-OPL-OLEI i. it. wherein R and R are hydrogen or short chain alkyl, where n-is an integer greater than 3, and where R is a residue of a monomeric organic compound having an active hydrogen, cg. alcohols, phenols, amides, primary amines, secondary amines, carboxylic acids, etc. These non-ionic detergents are well known (note US. 1,970,578 and U.S. 2,213,477) and may be typified by the polyalkylene oxide derivatives (i.e. polyethylene oxide, polypropylene oxide, polybutylene oxide) of water-insoluble higher fatty acids, such as lauric, oleic, palmitic and stearic acid and the like or mixtures thereof, such as the mixtures of fatty acids, obtained from animal and vegetable fats and oils or by oxidation of petroleum fractions such as paraflin wax. They may also be exemplified by the polyalkylene oxide derivatives of such water-insoluble organic hydroxy compounds as higher aliphatic alcohols- (i.e. the alcohols corresponding to the fatty acids specified above or mixtures thereof), oil or phenols, particularly alkyl phenols containing at least six alkyl carbon atoms such as isooctyl-, di-tertiary butyl-, triisopropyl-, nonyl-, dodecyl-, octadecylphenols or naphthols, or higher alkyl alcohols, such as benzyl alcohol, cinnamyl alcohol. They may also be exemplified by the polyalkylene oxide derivatives of such amines as stearyl, lauryl, dicyclohexyl, dibutyl amine and the like. A particularly useful nonionic detergent is that obtained by condensing one moi of tall oil with 5 to mols of ethylene oxide (See US. 2,550,691).

The nitroalkyl dichlorocarbanilates are also useful in preparing bacteriostatic cleansing compositions cornpounded from mixtures of detergents plus other ingredients as illustrated by the following compositions:

Composition A: Parts by weight Triethanol amine lauryl sulfate 6O Methyl cellulose 2 Propylene glycol 4 Potassium stearate 6 Water 130 I-(Z-nitrobutyl)3,4-dich1orocarbanilate 1 Composition B: Parts by Weight The nitroalkyl dichlorocarbanilates of this invention may be employed in cosmetic compositions ordinarily used to beautify, cleanse or protect the skin in any amount sufficient to inhibit the growth of or to kill bacteria, specifically Micrococcns pyogenes var. aurenus, normally present on the skin. Relatively small amounts of the nitroalkyl dichlorocarbanilates of this invention in cosmetics, particularly those having as a base an anionic or non-ionic organic detergent base composition or combination of said detergents, have been found to yield etlective bacteriostatic compositions. With respect to cosmetics having an anionic or non-ionic detergent base amounts as low as 0.1% to 1% by weight based upon the total weight of the organic detergent may be employed. It is preferred in detergent cleansing compositions having an anionic detergent base or non-ionic detergent base to employ these nitroalkyl dichlorocarbanilates in amounts in the order of 1% weight of detergent. While larger amounts up to 10% and even 50% by Weight of the detergent base may be employed, the upper limit will be determined by practical considerations as well as by the particular cosmetic composition involved, i.e. Whether the composition is to be used for cleansing purposes in the sense of a toilet soap or as a shaving cream or as a shampoo, etc. In cleansing compositions in the sense of a toilet soap containing an to 3% by weight based on the total r anionic organic detergent base (e.g. an alkali metal fatty acid detergent soap alone or in admixture with another anionic organic detergent such as the aforedescribed sodium alkyl aryl sulfonate detergents) or non-ionic detergent base, the amount of nitroalkyl dichlorocarbanilates of this invention ordinarily will not exceed 10% by Weight of the detergent base. However, in shampoos, shaving creams, and the like, employing an anionic organic detergent base or non-ionic detergent base the amounts of nitroalkyl dichlorocarbanilates of this invention may be present to the extent of by weight based on the total detergent base content. Various colors, antioxidants, perfumes, Water-softeners, salts such as silicates, chlorides, carbonates, phosphates and sulfates of alkali metals and the like builders, sodium carboxy methyl cellulose, the low molecular Weight alcohols such as methanol, ethanol, isopropanol, ethylene glycol, and the like, may be included Where desirable.

1. A compound of the formula o X NHC Where X is a halogen selected from the group consisting of chlorine and bromine, Y is a member selected from the group consisting of hydrogen, chlorine and bromine,

and Q is mononitroalkyl having from 3 to 8 carbon atoms.

2. A compound of the formula Where Q is mononitroalkyl having from 3 to 8 carbon atoms.

3. 1-(2-nitrobutyl) 3,4-dichlorocarbanilate.

4. 1-(Z-methyl-Z-nitropropyl) 3,4-dichlorocarbanilate.

5. 3-(2-methyl-2-nitrohexyl) hexyl 3,4-dichlorocarbanilate.

6. 4-(3-nitroheptyl) 3,4-dichlorocarbanilate.

7. 4-(5-nitrooctyl) 3,4dichlorocarbanilate.

References Cited in the file of this patent UNITED STATES PATENTS 2,487,799 Gump Nov. 15, 1949 2,535,077 Kunz et al Dec' 26, 1950 2,734,911 Strain 2 Feb. 14, 1956 2,789,129 Bissinger Apr. 16, 1957 2,850,524 MoWry et al. Sept. 2, 1958 2,858,328 Beaver et al Oct. 28, 1958 rUNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No 3,029,,273 April 10, 1962 David J, Beaver et a1.

It is hereby certified that error appears in the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.

Column 2, EXAMPLE IV, in the heading, line 33, strike out "Butyl" in italics; column 2 line 37, strike out "butyl"; column 3, TABLE 1, column 1, lines 9 and 10 thereof, for "4-4-dichlorocarbanilate" read 4-dichlorocarbanilate column 5, line 37, for "aurenus", in italics, read aureus in italics column 6, line 45 strike out "hexyl".

Signed and sgaled this 28th day of August 1962.

(SEAL) Attest:

ESTON G. JOHNSON DAVID L, LADD Attesting Officer Commissioner of Patents 

1. A COMPOUND OF THE FORMULA 